7LX5
The SARS-CoV-2 spike protein receptor binding domain bound to neutralizing nanobodies WNb 2 and WNb 10
Summary for 7LX5
| Entry DOI | 10.2210/pdb7lx5/pdb |
| EMDB information | 23566 |
| Descriptor | Spike glycoprotein, WNb 2, WNb 10 (3 entities in total) |
| Functional Keywords | sars-cov-2, nanobody cocktail, coronavirus spike, neutralizing nanobody, viral protein |
| Biological source | Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2) More |
| Total number of polymer chains | 3 |
| Total formula weight | 179956.32 |
| Authors | Pymm, P.,Glukhova, A.,Tham, W.-H. (deposition date: 2021-03-03, release date: 2021-05-05, Last modification date: 2024-10-23) |
| Primary citation | Pymm, P.,Adair, A.,Chan, L.J.,Cooney, J.P.,Mordant, F.L.,Allison, C.C.,Lopez, E.,Haycroft, E.R.,O'Neill, M.T.,Tan, L.L.,Dietrich, M.H.,Drew, D.,Doerflinger, M.,Dengler, M.A.,Scott, N.E.,Wheatley, A.K.,Gherardin, N.A.,Venugopal, H.,Cromer, D.,Davenport, M.P.,Pickering, R.,Godfrey, D.I.,Purcell, D.F.J.,Kent, S.J.,Chung, A.W.,Subbarao, K.,Pellegrini, M.,Glukhova, A.,Tham, W.H. Nanobody cocktails potently neutralize SARS-CoV-2 D614G N501Y variant and protect mice. Proc.Natl.Acad.Sci.USA, 118:-, 2021 Cited by PubMed Abstract: Neutralizing antibodies are important for immunity against SARS-CoV-2 and as therapeutics for the prevention and treatment of COVID-19. Here, we identified high-affinity nanobodies from alpacas immunized with coronavirus spike and receptor-binding domains (RBD) that disrupted RBD engagement with the human receptor angiotensin-converting enzyme 2 (ACE2) and potently neutralized SARS-CoV-2. Epitope mapping, X-ray crystallography, and cryo-electron microscopy revealed two distinct antigenic sites and showed two neutralizing nanobodies from different epitope classes bound simultaneously to the spike trimer. Nanobody-Fc fusions of the four most potent nanobodies blocked ACE2 engagement with RBD variants present in human populations and potently neutralized both wild-type SARS-CoV-2 and the N501Y D614G variant at concentrations as low as 0.1 nM. Prophylactic administration of either single nanobody-Fc or as mixtures reduced viral loads by up to 10-fold in mice infected with the N501Y D614G SARS-CoV-2 virus. These results suggest a role for nanobody-Fc fusions as prophylactic agents against SARS-CoV-2. PubMed: 33893175DOI: 10.1073/pnas.2101918118 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.44 Å) |
Structure validation
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